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Evaluate Safety and Explore Efficacy of SMUP-IA-01 in Patients With Knee Osteoarthritis

Primary Purpose

Knee Osteoarthritis

Status

Completed

Phase

Phase 1

Locations

Korea, Republic of

Study Type

Interventional

Intervention

SMUP-IA-01(low-dose)

SMUP-IA-01(mid-dose)

SMUP-IA-01(high-dose)

About this trial

This is an interventional treatment trial for Knee Osteoarthritis focused on measuring human umbilical cord blood derived mesenchymal stem cells, Knee Osteoarthritis

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male and female over 19 years of age
Subject with knee osteoarthritis (OA) and were diagnosed K&L grade 2 or 3 in radioactive examination at time of screening
Subject with more than 40mm joint pain on the 100-mm VAS, at the time of screening
Subject who were diagnosed as knee osteoarthritis by American College of Rheumatology (ACR) guideline criteria, at the time of screening
Subject with Body mass index (BMI) ≤35 kg/m2 at the time of screening
Subject with ligament instability ≤Grade II (grade o: no ligament instability, grade I: 0 ~ 5㎜, grade Ⅱ: 5 ~ 10 ㎜, grade Ⅲ: > 10 ㎜) at the time of screening
Subject who agree to maintain contraception during study period
Subject who voluntarily agreed to participate in the study, and signed informed consent

Exclusion Criteria:

Subject with myocardial infarction, congestive heart failure, and other severe heart disease or hypertension (or medical history of hypertension) that are not controlled below 140/90mmHg even with treatment with more than three(3) antihypertensive drugs
Subject with serious medical conditions other than cardiovascular disease
Subject with, or with a medical history of auto-immune diseases
Subject with an infection that requires parenteral antibiotic administration.
Subject with a medical history of mental disorder or epilepsy
Subject with chronic inflammatory joint diseases such as rheumatoid arthritis (e.g., osteoarthritis with infectious joint disease, gouty arthritis, and osteoarthritis)
Subject who had surgery or radiation therapy on knee joint area, or have not recovered from side effects of knee joint surgery within 12 weeks before screening
Subject who are pregnant or lactating
Subject abuse alcohol 10 times a week or smoke 25 cigarettes a day
Subject who were diagnosed with cancer within 5 years before screening
Subject who particiapted in another clinical trial within 4 weeks before screening of this clinical trial
Subject who were administered with immunosuppressnats such as cyclosporin A or azathioprine within 6 weeks before screening
Subject who had intra-articular administration such as sodium hyaluronate injections within 6 month before screening
Subject who are suffering from skin disease or considered inappropriate for injection in the injection site
Subject who has history of allergic response to hyaluronate injections or DMSO (cryopreservative) or Gentamicin (antibiotics)
Subject who are consiered inappropriate for MRI assessment with Tesla higher than 3.0
Subject with medical history of cell therapy product administration or are scheduled to administer other cell therapy product
Subject who principal investigator (PI) considers inappropriate to participate in the study due to any reasons other than those listed above

Sites / Locations

Seoul National University Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

SMUP-IA-01(low-dose)

SMUP-IA-01(mid-dose)

SMUP-IA-01(high-dose)

Arm Description

A single knee administration of SMUP-IA-01 (low-dose, 4.0 x 10^6 cells/2mL) (2 ml of 1% sodium hyaluronate injection is administered before administration of SMUP-IA-01)

A single knee administration of SMUP-IA-01 (mid-dose, 1.0 x 10^7 cells/2mL) ( 2 ml of 1% sodium hyaluronate injection is administered before administration of SMUP-IA-01)

A single knee administration of SMUP-IA-01 (high-dose, 2.0 x 10^7 cells/2mL) (2 ml of 1% sodium hyaluronate injection is administered before administration of SMUP-IA-01)

Outcomes

Primary Outcome Measures

Change of total score in WOMAC (Western Ontario and McMaster University Osteoarthritis Index) compared to baseline at 6 months after treatment

Change of total scorein WOMAC compared to baseline at 6 months after treatment. WOMAC consists of three subscales: pain, stiffness, and physical function, and is performed on baseline (visit 2) and final (Visit 8) visits. Total of 24 questions are evaluated with 5 questions for pain, 2 questions for stiffness, and 17 questions for physical function. Each question is scored between 0 point (no symptom) ~ 4 points (severe symptoms) scale, and the total score is between 0 point (no symptoms) ~ 96 points (higher score representing worse symptoms).

Secondary Outcome Measures

Change of score in WOMAC three subscales (Pain, stiffness, physical function)compared to baseline at 6 months after treatment

The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68).

Change of score in 100 mm VAS (Visual Analogue Scale) compared to baseline

The VAS is a horizontal line, 100 mm in length and anchored by word descriptors at each end (no pain, very severe pain). The patient marks on the line at the point that represents their current state. The VAS score is determined by measuring in millimeters from the left hand end to the point of the mark. The score ranges from "0" or no pain to "100" very severe pain.

Change of score in IKDC(International Knee Documentation Committee)compared to baseline

Change of score in IKDC compared to baseline. IKDC subjective knee evaluation consists of three categories: symptoms, sports activities, and functions. For each category, there are 7 questions for symptoms, 2 questions for sports activities, and 2 questions for functions, a total of 11 questions for evaluation. The scores for each category are summed up and divided into 87, which is the maximum score possible, and then is evaluated by converting it into a scale of 100 points. Higher score indicates better function and less symptoms for the knee.

Change of score in WORMS(Whole-Organ Magnetic Resonance iMaging Score) compared to baseline at 6 months after treatment

For structural and tissue evaluation of knee, MRI image of detailed knee parts are graded from min. 0 to max. 6. Lower number indicate normal status

Change in K&L(Kellgren-Lawrence) grade compared to the baseline at 3 months and 6 months after treatment

The K & L grade is 0 to 4 Grade, which means that the higher the grade, the greater the joint damage and the stenosis of the joint.

Change in joint space width compared to the baseline at 3 months and 6 months after treatment

Evaluation of disease progression in target knee as ascertained by change from baseline in joint space width (JSW) determined using radiography

Change in mechanical axis, anatomical axis compared to the baseline at 3 months and 6 months after treatment

The degree of deformation of the lower half of the body is measured by measuring the angles of the mechanical axis and the anatomical axis with respect to the vertical axis. Mechanical axis: A line connecting the femoral head center point and the ankle joint center point. Anatomical axis: The middaphyseal line of the femur and tibia.

Full Information

NCT ID

NCT04037345

First Posted

July 17, 2019

Last Updated

February 22, 2021

Sponsor

Medipost Co Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT04037345

Brief Title

Evaluate Safety and Explore Efficacy of SMUP-IA-01 in Patients With Knee Osteoarthritis

Official Title

A Open, Single-center, Phase 1 Trial to Evaluate Safety and Explore Efficacy of SMUP-IA-01 in Patients With Knee Osteoarthritis

Study Type

Interventional

2. Study Status

Record Verification Date

August 2020

Overall Recruitment Status

Completed

Study Start Date

October 7, 2019 (Actual)

Primary Completion Date

November 12, 2020 (Actual)

Study Completion Date

November 12, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Medipost Co Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This clinical trial is performed with patients with knee osteoarthritis who were radiologically diagnosed with Kellgren-Lawrence (K&L) grade 2 or 3. Subjects who voluntarily signed consent form and met inclusion/exclusion criteria, were evaluated eligible and participated in this trial. Investigator selected knee to be evaluated (right or left) and administered investigational product to selected knee on Day 1. A total of 3 or 6 subjects will be enrolled in low-dose or mid-dose group each, and 6 subjects will be enrolled in high-dose group. The study used a dose escalation scheme (from low-dose to high-dose) to determine the maximum tolerated dose (MTD).

Detailed Description

All subjects in each dose-group will visit 1 month* (visit 5, 1 month±5 days) after administration of investigational product to evaluate dose limit toxicity (DLT) and determine whether to drop or proceed to next dose level. Total 5 visit (1week, 1 month, 2 months, 3 months, 6 months) until 6 months after administration of investigational product is planned to assess safety through vial sign, laboratory tests, and exploratory efficacy of IP will be assessed through Western Ontario and McMaster Universities osteoarthritis index (WOMAC), 100-mm visual analogue scale (VAS) and International Knee Documentation Committee (IKDC) subjective knee evaluation.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Knee Osteoarthritis

Keywords

human umbilical cord blood derived mesenchymal stem cells, Knee Osteoarthritis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

SMUP-IA-01(low-dose)

Arm Type

Experimental

Arm Description

A single knee administration of SMUP-IA-01 (low-dose, 4.0 x 10^6 cells/2mL) (2 ml of 1% sodium hyaluronate injection is administered before administration of SMUP-IA-01)

Arm Title

SMUP-IA-01(mid-dose)

Arm Type

Experimental

Arm Description

A single knee administration of SMUP-IA-01 (mid-dose, 1.0 x 10^7 cells/2mL) ( 2 ml of 1% sodium hyaluronate injection is administered before administration of SMUP-IA-01)

Arm Title

SMUP-IA-01(high-dose)

Arm Type

Experimental

Arm Description

A single knee administration of SMUP-IA-01 (high-dose, 2.0 x 10^7 cells/2mL) (2 ml of 1% sodium hyaluronate injection is administered before administration of SMUP-IA-01)

Intervention Type

Biological

Intervention Name(s)

SMUP-IA-01(low-dose)

Other Intervention Name(s)

Human umbilical cord blood-derived mesenchymal stem cells

Intervention Description

A single knee administration of SMUP-IA-01(low-dose, 4.0 x 10^6 cells/2mL)

Intervention Type

Biological

Intervention Name(s)

SMUP-IA-01(mid-dose)

Other Intervention Name(s)

Human umbilical cord blood-derived mesenchymal stem cells

Intervention Description

A single knee administration of SMUP-IA-01(mid-dose, 1.0 x 10^7 cells/2mL)

Intervention Type

Biological

Intervention Name(s)

SMUP-IA-01(high-dose)

Other Intervention Name(s)

Human umbilical cord blood-derived mesenchymal stem cells

Intervention Description

A single knee administration of SMUP-IA-01(high-dose, 2.0 x 10^7 cells/2mL)

Primary Outcome Measure Information:

Title

Change of total score in WOMAC (Western Ontario and McMaster University Osteoarthritis Index) compared to baseline at 6 months after treatment

Description

Time Frame

Baseline, Month 6

Secondary Outcome Measure Information:

Title

Change of score in WOMAC three subscales (Pain, stiffness, physical function)compared to baseline at 6 months after treatment

Description

The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68).

Time Frame

Baseline, Month 6

Title

Change of score in 100 mm VAS (Visual Analogue Scale) compared to baseline

Description

Time Frame

Baseline, Month 1, Month 2, Month 3, Month 6

Title

Change of score in IKDC(International Knee Documentation Committee)compared to baseline

Description

Time Frame

Baseline, Month 1, Month 2, Month 3, Month 6

Title

Change of score in WORMS(Whole-Organ Magnetic Resonance iMaging Score) compared to baseline at 6 months after treatment

Description

For structural and tissue evaluation of knee, MRI image of detailed knee parts are graded from min. 0 to max. 6. Lower number indicate normal status

Time Frame

Baseline, Month 6

Title

Change in K&L(Kellgren-Lawrence) grade compared to the baseline at 3 months and 6 months after treatment

Description

The K & L grade is 0 to 4 Grade, which means that the higher the grade, the greater the joint damage and the stenosis of the joint.

Time Frame

Baseline, Month 3, Month 6

Title

Change in joint space width compared to the baseline at 3 months and 6 months after treatment

Description

Evaluation of disease progression in target knee as ascertained by change from baseline in joint space width (JSW) determined using radiography

Time Frame

Baseline, Month 3, Month 6

Title

Change in mechanical axis, anatomical axis compared to the baseline at 3 months and 6 months after treatment

Description

Time Frame

Baseline, Month 3, Month 6

10. Eligibility

Sex

All

Minimum Age & Unit of Time

19 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male and female over 19 years of age Subject with knee osteoarthritis (OA) and were diagnosed K&L grade 2 or 3 in radioactive examination at time of screening Subject with more than 40mm joint pain on the 100-mm VAS, at the time of screening Subject who were diagnosed as knee osteoarthritis by American College of Rheumatology (ACR) guideline criteria, at the time of screening Subject with Body mass index (BMI) ≤35 kg/m2 at the time of screening Subject with ligament instability ≤Grade II (grade o: no ligament instability, grade I: 0 ~ 5㎜, grade Ⅱ: 5 ~ 10 ㎜, grade Ⅲ: > 10 ㎜) at the time of screening Subject who agree to maintain contraception during study period Subject who voluntarily agreed to participate in the study, and signed informed consent Exclusion Criteria: Subject with myocardial infarction, congestive heart failure, and other severe heart disease or hypertension (or medical history of hypertension) that are not controlled below 140/90mmHg even with treatment with more than three(3) antihypertensive drugs Subject with serious medical conditions other than cardiovascular disease Subject with, or with a medical history of auto-immune diseases Subject with an infection that requires parenteral antibiotic administration. Subject with a medical history of mental disorder or epilepsy Subject with chronic inflammatory joint diseases such as rheumatoid arthritis (e.g., osteoarthritis with infectious joint disease, gouty arthritis, and osteoarthritis) Subject who had surgery or radiation therapy on knee joint area, or have not recovered from side effects of knee joint surgery within 12 weeks before screening Subject who are pregnant or lactating Subject abuse alcohol 10 times a week or smoke 25 cigarettes a day Subject who were diagnosed with cancer within 5 years before screening Subject who particiapted in another clinical trial within 4 weeks before screening of this clinical trial Subject who were administered with immunosuppressnats such as cyclosporin A or azathioprine within 6 weeks before screening Subject who had intra-articular administration such as sodium hyaluronate injections within 6 month before screening Subject who are suffering from skin disease or considered inappropriate for injection in the injection site Subject who has history of allergic response to hyaluronate injections or DMSO (cryopreservative) or Gentamicin (antibiotics) Subject who are consiered inappropriate for MRI assessment with Tesla higher than 3.0 Subject with medical history of cell therapy product administration or are scheduled to administer other cell therapy product Subject who principal investigator (PI) considers inappropriate to participate in the study due to any reasons other than those listed above

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Myungchul Lee, MD, PhD

Organizational Affiliation

Seoul National University Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Seoul National University Hospital

City

Seoul

State/Province

Jongno-gu

ZIP/Postal Code

03080

Country

Korea, Republic of

12. IPD Sharing Statement

Learn more about this trial

Evaluate Safety and Explore Efficacy of SMUP-IA-01 in Patients With Knee Osteoarthritis

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